ARBIOS developed a novel hybrid bioartificial live r(HyBAL) to treat patients with liver failure of various etiologies. In the absence of any other alternative, such patients must receive a liver transplant or endure prolonged hospitalization. In treating acute liver failure it is critical to provide whole liver functions. It is believed that liver support at this level of complexity requires utilization of viable isolated liver cells. Our own argument, which dates back to the development of our first-generate bioartificial liver, is that a truly effective system should be a hybrid one, i.e., it should combine liver cell therapy and detoxification using sorbents (e.g., activated charcoal, exchange resin). The HYBAL is the first liver assist system in which these two functions are integrated in a single molecule. Depending on the cause of liver disease, severity of illness and deficiency of specific liver functions, these modes of therapy can be provided individually, simultaneously or sequentially. In addition, the HYBAL's basic commercially available kidney dialysis platform represents a major improvement in efficiency with a concomitant reduction in cost and complexity compared to other existing systems. The goal of this proposal is to validate the HyBAL concept. The prototype HyBAL devices will utilize matrix-anchored rat or pig hepatocytes and sorbents (charcoal and exchange resin particles). They will e perfused for 8 hours with plasma removed with pigs with surgically-induced fulminant hepatic failure(FHF). Changes in plasma levels of ammonia, urea, bilirubin and other liver-specific parameters will be monitored. In addition, the HyBAL will be challenged with exogenous ammonium chloride, galactose and lidocaine. In vivo, he ability of HyBAL to support pigs with FHF will be examined. In both experimental settings, HyBAL devices from which either cell therapy or sorbents have been omitted, will be tested to determine the respective role of cell and sorption therapy in the overall HyBAL performance. PROPOSED COMMERCIAL APPLICATIONS: The National Center for Health Statistics (NCHS) reported that in 1999, over 250,000 patients underwent 340,000 hospitalizations due to acute liver failure; 43,000 patients died (7th leading cause of death). Based on these data, NCHS estimates that more than 200,000 liver support treatments are needed annually in the U.S. lone to keep liver failure patients alive until an organ becomes available for transplantation or the native liver recovers from injury ($1.5-billion market).